title: Coumarin compounds of Biebersteinia multifida roots show potential anxiolytic effects in mice.
abstract: BACKGROUND
  Traditional preparations of the root of Biebersteinia multifida DC (Geraniaceae), a native medicinal plant of Irano-Turanian floristic region, have been used for the treatment of phobias as anxiolytic herbal preparation.
  
  
  METHODS
  We utilized the phobic behavior of mice in an elevated plus-maze as a model to evaluate the anxiolytic effect of the plant extract and bio-guided fractionation was applied to isolate the active compounds. Total root extract, alkaline and ether fraction were administered to mice at different doses 30 and 90 min prior to the maze test. Saline and diazepam were administered as negative and positive controls, respectively. The time spent in open and closed arms, an index of anxiety behavior and entry time, was measured as an index of animal activity.
  
  
  RESULTS
  The total root extract exhibited anxiolytic effect which was comparable to diazepam but with longer duration. This sustained effect of the crude extract was sustained for 90 min and was even more after injection of 45 mg/kg while the effect of diazepam had been reduced by 90 min. The anxiolytic effect factor was only present in the alkaline fraction and displayed its effect at lower doses than diazepam while pure vasicinone as the previously known alkaloid did not shown anxiolytic effect. The effect of the alkaline fraction was in a dose dependent manner starting at 0.2 mg/kg with a maximum at 1.0 mg/kg. Bio-guided fractionation using a variety of chromatographic methods led to isolation and purification of three coumarin derivatives from the bioactive fraction, including umbelliferone, scopoletin, and ferulic acid.
  
  
  CONCLUSIONS
  For the first time, bio-guided fractionation of the root extract of B. multifida indicates significant sustained anxiolytic effects which led to isolation of three coumarin derivatives with well-known potent MAO inhibitory and anti-anxiety effects. These data contribute to evidence-based traditional use of B. multifida root for anxiety disorders.
authors.forename: Hamid Reza
authors.initials: HR
authors.lastname: Monsef-Esfahani
authors.forename: Mohsen
authors.initials: M
authors.lastname: Amini
authors.forename: Navid
authors.initials: N
authors.lastname: Goodarzi
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Saiedmohammadi
authors.forename: Reza
authors.initials: R
authors.lastname: Hajiaghaee
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Faramarzi
authors.forename: Zahra
authors.initials: Z
authors.lastname: Tofighi
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Ghahremani
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy*; D002853:Chromatography, Liquid; D003373:Coumaric Acids / Q000008:administration & dosage / Q000627:therapeutic use; D003374:Coumarins / Q000008:administration & dosage* / Q000627:therapeutic use; D003975:Diazepam / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D031314:Geraniaceae / Q000737:chemistry*; D006801:Humans; D008297:Male; D051379:Mice; D010936:Plant Extracts / Q000008:administration & dosage* / Q000627:therapeutic use; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D012603:Scopoletin / Q000008:administration & dosage / Q000627:therapeutic use; D014468:Umbelliferones / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D014151:Anti-Anxiety Agents; D003373:Coumaric Acids; D003374:Coumarins; D010936:Plant Extracts; D014468:Umbelliferones; C031477:7-hydroxycoumarin; C004999:ferulic acid; D012603:Scopoletin; D003975:Diazepam